CA3131223C - Compositions for inhibiting masp-2 dependent complement activation - Google Patents
Compositions for inhibiting masp-2 dependent complement activation Download PDFInfo
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- CA3131223C CA3131223C CA3131223A CA3131223A CA3131223C CA 3131223 C CA3131223 C CA 3131223C CA 3131223 A CA3131223 A CA 3131223A CA 3131223 A CA3131223 A CA 3131223A CA 3131223 C CA3131223 C CA 3131223C
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- C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
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- C07K2317/00—Immunoglobulins specific features
- C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
- C07K2317/56—Immunoglobulins specific features characterized by immunoglobulin fragments variable (Fv) region, i.e. VH and/or VL
- C07K2317/565—Complementarity determining region [CDR]
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- C07K2317/62—Immunoglobulins specific features characterized by non-natural combinations of immunoglobulin fragments comprising only variable region components
- C07K2317/622—Single chain antibody (scFv)
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- C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
- C07K2317/76—Antagonist effect on antigen, e.g. neutralization or inhibition of binding
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- C—CHEMISTRY; METALLURGY
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- C07K2317/90—Immunoglobulins specific features characterized by (pharmaco)kinetic aspects or by stability of the immunoglobulin
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Families Citing this family (46)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| HUE029635T2 (en) | 2007-09-26 | 2017-03-28 | Chugai Pharmaceutical Co Ltd | A method for modifying an isoelectric point of an antibody by amino acid substitution in CDR |
| DK2708559T3 (en) | 2008-04-11 | 2018-06-14 | Chugai Pharmaceutical Co Ltd | Antigen-binding molecule capable of repeatedly binding two or more antigen molecules |
| TWI812066B (zh) | 2010-11-30 | 2023-08-11 | 日商中外製藥股份有限公司 | 具有鈣依存性的抗原結合能力之抗體 |
| CA3076975C (en) | 2011-04-08 | 2024-06-18 | Omeros Corporation | Methods for treating conditions associated with masp-2 dependent complement activation |
| US9644035B2 (en) | 2011-04-08 | 2017-05-09 | Omeros Corporation | Methods for treating conditions associated with MASP-2 dependent complement activation |
| CA3131223C (en) * | 2011-05-04 | 2024-01-30 | Omeros Corporation | Compositions for inhibiting masp-2 dependent complement activation |
| JP6774164B2 (ja) | 2012-08-24 | 2020-10-21 | 中外製薬株式会社 | マウスＦｃγＲＩＩ特異的Ｆｃ抗体 |
| JP6538561B2 (ja) | 2012-10-25 | 2019-07-03 | バイオベラティブ・ユーエスエイ・インコーポレイテッド | 抗補体Ｃ１ｓ抗体とそれらの用途 |
| EP2914291B1 (en) | 2012-11-02 | 2022-02-23 | Bioverativ USA Inc. | Anti-complement c1s antibodies and uses thereof |
| CA2906096C (en) | 2013-03-15 | 2022-03-15 | Omeros Corporation | Methods of generating bioactive peptide-bearing antibodies and compositions comprising the same |
| US20140363433A1 (en) | 2013-03-15 | 2014-12-11 | Omeros Corporation | Methods of Generating Bioactive Peptide-bearing Antibodies and Compositions Comprising the Same |
| TWI636062B (zh) | 2013-04-02 | 2018-09-21 | 中外製藥股份有限公司 | Fc region variant |
| SI3057993T1 (sl) * | 2013-10-17 | 2021-03-31 | Omeros Corporation | Postopki za zdravljenje bolezenskih stanj, povezanih z aktivacijo komplementov, odvisnih od MASP-2 |
| TWI779010B (zh) | 2014-12-19 | 2022-10-01 | 日商中外製藥股份有限公司 | 抗肌抑素之抗體、含變異Ｆｃ區域之多胜肽及使用方法 |
| EP3253778A1 (en) | 2015-02-05 | 2017-12-13 | Chugai Seiyaku Kabushiki Kaisha | Antibodies comprising an ion concentration dependent antigen-binding domain, fc region variants, il-8-binding antibodies, and uses therof |
| PL3280440T3 (pl) | 2015-04-06 | 2023-06-19 | Bioverativ Usa Inc. | Humanizowane przeciwciała anty-c1s i sposoby ich zastosowania |
| CN106699888B (zh) | 2015-07-28 | 2020-11-06 | 上海昀怡健康科技发展有限公司 | 一种pd-1抗体及其制备方法和应用 |
| SG10202011469UA (en) | 2015-11-09 | 2020-12-30 | Omeros Corp | Methods for treating conditions associated with masp-2 dependent complement activation |
| EP3394098A4 (en) | 2015-12-25 | 2019-11-13 | Chugai Seiyaku Kabushiki Kaisha | ANTI-MYOSTATIN ANTIBODIES AND METHODS OF USE |
| CN117503923A (zh) * | 2016-01-05 | 2024-02-06 | 莱斯特大学 | 用于抑制有需要的受试者的纤维化的方法 |
| IL305200A (en) * | 2016-03-31 | 2023-10-01 | Omeros Corp | MASP-2 suppressing agents for use in suppressing angiogenesis |
| JOP20170154B1 (ar) * | 2016-08-01 | 2023-03-28 | Omeros Corp | تركيبات وطرق لتثبيط masp-3 لعلاج أمراض واضطرابات مختلفة |
| KR102538749B1 (ko) | 2016-08-05 | 2023-06-01 | 추가이 세이야쿠 가부시키가이샤 | Il-8 관련 질환의 치료용 또는 예방용 조성물 |
| JOP20170170B1 (ar) * | 2016-08-31 | 2022-09-15 | Omeros Corp | صيغ لجسم مضاد تثبيطية لـ masp-2 بتركيز عالي ولزوجة منخفضة وأطقم، وطرق |
| SG10201607778XA (en) | 2016-09-16 | 2018-04-27 | Chugai Pharmaceutical Co Ltd | Anti-Dengue Virus Antibodies, Polypeptides Containing Variant Fc Regions, And Methods Of Use |
| JOP20190068A1 (ar) * | 2016-10-13 | 2019-04-01 | Omeros Corp | طرق لتقليل البول البروتيني في خاضع بشري يعاني من الاعتلال الكلوي a الناتج عن الجلوبيولين المناعي |
| TW202402809A (zh) * | 2017-08-15 | 2024-01-16 | 美商歐米諾斯公司 | 用於治療和／或預防與造血幹細胞移植有關的移植物抗宿主病和／或瀰漫性肺泡出血和／或靜脈閉塞性病的方法 |
| CA3072913A1 (en) * | 2017-08-25 | 2019-02-28 | Omeros Corporation | Highly concentrated low viscosity masp-2 inhibitory antibody formulations, kits, and methods of treating subjects suffering from atypical hemolytic syndrome |
| CA3093729A1 (en) | 2018-03-15 | 2019-09-19 | Chugai Seiyaku Kabushiki Kaisha | Anti-dengue virus antibodies having cross-reactivity to zika virus and methods of use |
| BR112020024148A2 (pt) * | 2018-05-29 | 2021-03-30 | Omeros Corporation | Compostos, composição farmacêutica, e, métodos para identificação de uma pequena molécula capaz de inibir masp-2 e para o tratamento de uma doença ou transtorno associado a masp-2 |
| US11584714B2 (en) | 2018-05-29 | 2023-02-21 | Omeros Corporation | MASP-2 inhibitors and methods of use |
| LT3893924T (lt) * | 2018-12-13 | 2024-10-10 | argenx BV | Antikūnai žmogaus komplemento faktoriui c2b ir jų panaudojimo būdai |
| CA3159167A1 (en) | 2019-12-04 | 2021-06-10 | Neil S. Cutshall | Masp-2 inhibitors and methods of use |
| CA3159176A1 (en) | 2019-12-04 | 2021-06-10 | Neil S. Cutshall | Masp-2 inhibitors and methods of use |
| WO2021113698A1 (en) | 2019-12-04 | 2021-06-10 | Omeros Corporation | Masp-2 inhibitors and methods of use |
| JP2023504543A (ja) | 2019-12-04 | 2023-02-03 | オメロス コーポレーション | Ｍａｓｐ－２阻害剤および使用方法 |
| TWI834025B (zh) * | 2020-03-06 | 2024-03-01 | 美商奥默羅斯公司 | 用於治療和/或預防冠狀病毒誘導的急性呼吸窘迫症候群的抑制masp-2的方法 |
| CN114634575A (zh) * | 2020-12-16 | 2022-06-17 | 康诺亚生物医药科技（成都）有限公司 | 一种补体抑制剂的开发和应用 |
| IL304927A (en) * | 2021-02-05 | 2023-10-01 | Omeros Corp | A biomarker for assessing the risk of developing acute COVID-19 and post-acute COVID-19 |
| CN115215937B (zh) * | 2021-04-15 | 2023-05-26 | 上海麦济生物技术有限公司 | 抗人masp-2抗体及其制备方法和应用 |
| JP2024518724A (ja) | 2021-04-25 | 2024-05-02 | 江▲蘇▼恒瑞医▲薬▼股▲フン▼有限公司 | 抗ｍａｓｐ２抗体、その抗原結合断片および医薬用途 |
| CN116615544A (zh) * | 2021-12-10 | 2023-08-18 | 舒泰神（北京）生物制药股份有限公司 | 特异性识别masp2的抗体及其应用 |
| CA3240483A1 (en) | 2021-12-10 | 2023-06-15 | Thomas Dudler | Therapeutic antibodies that bind to the serine protease domain of masp-2 and uses thereof |
| CN116284412A (zh) * | 2021-12-21 | 2023-06-23 | 沈阳三生制药有限责任公司 | 一种抗masp-2抗体及其制备方法与用途 |
| WO2023174039A1 (en) * | 2022-03-18 | 2023-09-21 | Inmagene Biopharmaceuticals (Hangzhou) Co., Ltd. | Masp-2-targetting antibodies and uses thereof |
| US20240228499A1 (en) | 2022-11-30 | 2024-07-11 | Omeros Corporation | Masp-2 inhibitors and methods of use |
Family Cites Families (35)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4816567A (en) | 1983-04-08 | 1989-03-28 | Genentech, Inc. | Recombinant immunoglobin preparations |
| US5211657A (en) | 1988-11-07 | 1993-05-18 | The United States Government As Represented By The Secretary Of The Department Of Health And Human Services | Laminin a chain deduced amino acid sequence, expression vectors and active synthetic peptides |
| US5549910A (en) | 1989-03-31 | 1996-08-27 | The Regents Of The University Of California | Preparation of liposome and lipid complex compositions |
| US5859205A (en) * | 1989-12-21 | 1999-01-12 | Celltech Limited | Humanised antibodies |
| JP3218637B2 (ja) | 1990-07-26 | 2001-10-15 | 大正製薬株式会社 | 安定なリポソーム水懸濁液 |
| JP2958076B2 (ja) | 1990-08-27 | 1999-10-06 | 株式会社ビタミン研究所 | 遺伝子導入用多重膜リポソーム及び遺伝子捕捉多重膜リポソーム製剤並びにその製法 |
| US5856121A (en) | 1994-02-24 | 1999-01-05 | Case Western Reserve University | Growth arrest homebox gene |
| JPH07238100A (ja) | 1994-02-25 | 1995-09-12 | Sumitomo Electric Ind Ltd | ヒトのｍａｓｐに対するモノクローナル抗体 |
| US5741516A (en) | 1994-06-20 | 1998-04-21 | Inex Pharmaceuticals Corporation | Sphingosomes for enhanced drug delivery |
| US5795587A (en) | 1995-01-23 | 1998-08-18 | University Of Pittsburgh | Stable lipid-comprising drug delivery complexes and methods for their production |
| US5738868A (en) | 1995-07-18 | 1998-04-14 | Lipogenics Ltd. | Liposome compositions and kits therefor |
| BR9509985A (pt) | 1995-12-12 | 1998-11-03 | Omeros Med Sys Inc | Solução para irrigação e método para inibição de dor inflamação e esparmo |
| US7083786B2 (en) | 1997-04-03 | 2006-08-01 | Jensenius Jens Chr | MASP-2, a complement-fixing enzyme, and uses for it |
| JP2002532079A (ja) | 1998-12-15 | 2002-10-02 | ザ ブライハム アンド ウイミンズ ホスピタル， インコーポレイテッド | 補体活性化に関連するレクチン補体経路を調節するための方法および産物 |
| ATE399025T1 (de) | 1999-07-21 | 2008-07-15 | Omeros Corp | Spüllösungen und verfahren zur schmerzhemmung, entzündungshemmung und hemmung des knorpelabbaus |
| US20010051754A1 (en) | 1999-08-03 | 2001-12-13 | Daria N. Lissy | Plural stage toluene disproportionation process minimizing ethylbenzene |
| AU2001240020B9 (en) * | 2000-03-01 | 2008-12-04 | Medimmune, Llc | High potency recombinant antibodies and method for producing them |
| SG98393A1 (en) | 2000-05-19 | 2003-09-19 | Inst Materials Research & Eng | Injectable drug delivery systems with cyclodextrin-polymer based hydrogels |
| DK1303591T3 (da) * | 2000-07-13 | 2009-11-02 | Helion Biotech Aps | MASP-2, et komplementfikserende enzym, og anvendelser af det |
| DE60128914T2 (de) * | 2001-10-05 | 2008-05-08 | Affimed Therapeutics Ag | Antikörper menschlichen Ursprungs zur Hemmung der Thrombozytenaggregation |
| ES2645698T3 (es) * | 2001-11-30 | 2017-12-07 | Amgen Fremont Inc. | Animales transgénicos que portan genes de cadena ligera de Ig humana |
| CN1697647A (zh) | 2002-02-01 | 2005-11-16 | 奥默罗斯公司 | 用于抑制疼痛,炎症和软骨退化的溶液及方法 |
| JP4723244B2 (ja) | 2002-07-19 | 2011-07-13 | オメロス コーポレイション | 生分解性トリブロックコポリマー、その合成方法、ならびにそれから作製されるヒドロゲルおよび生体材料 |
| CA2515389A1 (en) * | 2003-02-28 | 2004-09-10 | Mitsubishi Pharma Corporation | Monoclonal antibody and gene encoding the same, hybridoma, pharmaceutical compostion, and diagnostic reagent |
| PT2374819T (pt) | 2003-05-12 | 2017-07-04 | Helion Biotech Aps | Anticorpos para masp-2 |
| US7919094B2 (en) * | 2004-06-10 | 2011-04-05 | Omeros Corporation | Methods for treating conditions associated with MASP-2 dependent complement activation |
| GB0412966D0 (en) | 2004-06-10 | 2004-07-14 | Univ Leicester | Genetically modified non-human mammals and cells |
| PT1753456T (pt) | 2004-06-10 | 2016-11-04 | Univ Leicester | Métodos para tratar condições associadas com a ativação do complemento dependente de masp-2 |
| WO2005123776A1 (en) | 2004-06-10 | 2005-12-29 | Omeros Corporation | Methods for treating conditions associated with lectin-dependent complement activation |
| US8840893B2 (en) | 2004-06-10 | 2014-09-23 | Omeros Corporation | Methods for treating conditions associated with MASP-2 dependent complement activation |
| US8192738B2 (en) | 2008-09-19 | 2012-06-05 | Medimmune, Llc | Targeted antibodies directed to DLL4 |
| EP2356270B1 (en) | 2008-11-07 | 2016-08-24 | Fabrus Llc | Combinatorial antibody libraries and uses thereof |
| PT2488203T (pt) * | 2009-10-16 | 2017-03-10 | Univ Leicester | Métodos para tratamento de coagulação intravascular disseminada através da inibição da activação do complemento dependente de masp-2 |
| CA3131223C (en) * | 2011-05-04 | 2024-01-30 | Omeros Corporation | Compositions for inhibiting masp-2 dependent complement activation |
| SI2833907T1 (en) * | 2012-04-06 | 2018-07-31 | Omeros Corporation | COMPOSITION AND METHODS OF INJECTION OF MASP-1 AND / OR MASP-3 FOR TREATMENT OF PAROXYSIMAL NIGHT CHEMOGLOBINURIA |
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- 2020-06-10 CY CY20201100525T patent/CY1123212T1/el unknown
- 2020-06-22 RU RU2020120539A patent/RU2020120539A/ru unknown
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2021
- 2021-08-10 IL IL285522A patent/IL285522A/en unknown
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2022
- 2022-09-02 JP JP2022139872A patent/JP2022172275A/ja not_active Withdrawn
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2023
- 2023-02-13 US US18/168,192 patent/US20240092938A1/en active Pending
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